uni'wissen 02-2013_ENG

Prof. Dr. Irmgard Merfort studied pharmacy at the University of Münster and earned her doctorate and habilitation qualification at the Institute of Pharmaceuti- cal Biology of the University of Düsseldorf. She has served as professor for pharmaceutical biology and biotechnology at the Insti- tute of Pharmaceutical Sci- ences of the University of Freiburg since 1995. She conducts research on agents with an anti-inflam- matory, anti-tumor, or wound-healing effect. These agents come from medicinal plants of Europe as well as Central and South America. In the EU- funded project Biocombust, she is studying the biologi- cal effects of particles cre- ated during the process of burning biomass. She has authored more than 140 publications, is co-editor of the journal Planta Medica, and is a member of the advi- sory board of the Journal of Ethnopharmacology. Photo: private wound healing. In addition, the scientists identi- fied several other proteins that play a role in these processes. Cells Migrate Faster with Birch Bark Extract In the second phase of wound healing, the cells need to multiply in the skin and close the gap created by the wound. In collaboration with a research group from the Institute of Molecular Medicine and Cell Research at the University of Freiburg, Merfort and her team conducted a test with a small dish full of human skin cells. The scientists inflicted an artificial wound on the keratinocytes by tearing into the cell layer. They then observed the wound under the mi- croscope for 24 hours to determine how quickly it closed with and without the birch bark extract. The result: The cells migrated into the artificial wound and closed it more quickly with the ex- tract. But how can this be explained? “When the cell begins to migrate, it changes its shape,” explains Merfort. The cell receives its shape from its skeleton, which consists of the struc- tural protein actin. It moves by contracting its so-called stress fibers, part of the cytoskeleton composed of actin, and pushing itself forward. In addition, various types of fibers form at the front and the back of the cell and help it seek contact with other cells. The substances tested by the scientists exert influence on the actin cy- toskeleton: “Even extremely low concentrations of birch bark extract or the isolated compo- nents betulin and lupeol cause the cell to form The birch substance exerts influence on the cyto- skeleton and causes more stress fibers, filopodia, and lamellipodia to form on its surface. They help the cells to migrate – and thus close wounds – more quickly. Photo: Irmgard Merfort more stress fibers. This explains why the kera- tinocytes migrate into the wound more quickly.” Merfort and her colleagues then teamed up with a research group at the Institute of Experi- mental and Clinical Pharmacology and Toxicol- ogy of the University of Freiburg to find the protein behind the effect they had observed. The researchers ascertained that the birch sub- stance and its components betulin and lupeol in- crease the concentrations of several proteins involved in the restructuring of the actin cyto- skeleton. This is particularly true of the protein RhoA, which plays an important role in the for- mation of the stress fibers. “We thus succeeded in explaining the therapeutic effect of birch bark extract on the molecular level. It was an exciting and interesting project that enabled us to strengthen traditional plant remedies,” says Mer- fort, delighted at the findings. In a follow-up proj- ect, the pharmaceutical researcher wants to study how the substances from the birch take ef- fect in wounds on diabetic patients. Further Reading Ebeling, S./Naumann, K./Pollok, S./Vidal-y-Sy, S./Wardecki, T./Nascimento, J. M./Boerries, M./Schmidt, G./Brandner, J. M./Merfort, I.: From a traditional medicinal plant to a rational drug: Understanding the clinically proven wound healing efficacy of birch bark extract. In: PLOS ONE (in press). Schempp, C./Huyke, C. (2005): Behandlung von Verbrennungen 2. Grades mit Birken- creme. In: Der Merkurstab 5/2005, p. 402. Woelfle, U./Laszczyk, M. N./Kraus, M./Leuner, K./Kersten, A./Simon-Haarhaus, B./Scheffler, A./ Martin, S. F./Müller, W. E./Nashan, D./ Schempp, C. (2010): Triterpenes promote kera- tinocyte differentiation in vitro, ex vivo and in vivo: A role for the transient receptor potential canonical (subtype) 6. In: Journal of Investiga- tive Dermatology 130/1, pp. 113–123. 27